A report on the anticonvulsant activity of a series of 5,5-disubstituted-2-pyrrolidinones designed as inhibitors of .gamma.-aminobutyric acid-.alpha.-ketoglutaric acid transaminase was published in Carvajal et al., Biochem Pharmacol. 13, 1059 (1964). Within this series, the 5-ethyl-5-phenyl compound showed a broad profile of anticonvulsant activity. It protects mice against seizures provoked by pentetrazol (pentylenetetrazol), maximal electroshock, and bicuculline, and cats against hippocampal kindling. See Perez-de-la-Mora et al., R. Biochem. Pharmacol. 22, 2635 (1973) and Solis et al., Neurobiologia, Symposium Internacional, pp. 83-94, (1979). It also shows a potent clinical antiepileptic action in patients having grand mal seizures. See, Carvajal, Gac. Med. Mex., 3, 196 (1976) .
Later studies using NMR spectroscopy and X-ray diffraction demonstrated that the compound which initially was thought to be 5-ethyl-5-phenylpyrrolidinone was in fact (.+-.)-4-hydroxy-4-phenylhexanamide (compound 3 in Table 1 below). See, Joseph-Nathan et al., Rev. Latinoamer, Quim. 9, 90 (1978); and Castellano et al., Acta Cryst. B37, 285 (1981). Several studies have been made of the mechanism of action of this compound (see Perez-de-la-Mora et al. cited above, and De-La-Cruz et al., Pharmacol. Biochem. Behav. 16, 117 (1982)), but at present this mechanism remains unknown. A need persists to identify other hydroxyamides having useful levels of anticonvulsant activity.